OVERVIEW OF OBESITY MANAGEMENT
Transcript of OVERVIEW OF OBESITY MANAGEMENT
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OVERVIEW OF OBESITY MANAGEMENT
Caroline M. Apovian, MD, FACN, FACP, FTOS, DABOMPast President, 2018The Obesity Society
Co-Director, Center for Weight Management and Wellness
Division of Endocrinology, Diabetes, and Hypertension
Brigham and Women’s Hospital
Faculty Member
Harvard Medical School
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Caroline M. Apovian, MD, FACN, FACP, FTOS, DABOM
• One of the founding creators of the American Board of Obesity Medicine (ABOM)
• Co-Director for the NIH-funded Boston Nutrition and Obesity Research Center (BNORC)
• President of The Obesity Society in 2017-2018
• Chair of the Endocrine Society Guidelines for Medical Treatment of Obesity, 2015
• Member of the expert panel for updating the 2013 AHA/ACC/TOS Clinical Guidelines for
the Management of Overweight and Obesity in Adults
• Former Nutrition Consultant for the National Aeronautics and Space Administration (NASA)
• Given over 200 invited lectures nationally and internationally
• Published over ten books and over 200 peer-reviewed original research and review articles
on obesity and nutrition
Current research interests are weight change and its effects on adipose tissue metabolism
and inflammation, obesity and cardiovascular disease, resolution of type 2 diabetes and
cardiovascular disease in the bariatric surgery population, disparities in the treatment of
obesity in underserved populations, and novel pharmacotherapeutic agents for the
treatment of obesity.
She is also an expert in sampling subcutaneous adipose tissue and muscle tissue in
humans and has been studying the relationship between adipose tissue inflammation and
obesity for over 15 years
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Disclosures• Consultant, Merck
• Consultant, Nutrisystem
• Consultant, Zafgen
• Consultant, Sanofi-Aventis
• Consultant, Orexigen
• Consultant EnteroMedics
• Consultant, Scientific Intake
• Consultant, Set Point health
• Consultant, Rhythm Pharmaceuticals
• Consultant, Xeno Biosciences
• Consultant, Gelesis
• Consultant, Ferring
• Consultant, Takeda
• Consultant, Novo Nordisk
• Research support, Aspire Bariatrics
• Research support, GI Dynamics
• Research support, Pfizer
• Research support, Gelesis
• Research support, Orexigen
• Research support, Meta Proteomics
• Research support, Takeda
• Research support, The Atkins Foundation
• Research support MYOS Corporation
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Objectives
• Identify the role of hormonal adaptation in weight management
• Name the newest anti-obesity FDA-approved medication and it’s mechanism of action
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U.S. Prevalence of Obesity, 2017-2018
https://www.cdc.gov/nchs/products/databriefs/db360.htm
Adults > 20 years, Obesity = BMI > 30
42.4%TOTAL
43%MEN
41.9%WOMEN
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42.4%ObesityBMI > 30
9.2%Severe ObesityBMI > 40
30.7% OverweightBMI = 25-29.9
U.S. Trends in Overweight, Obesity, and Severe ObesityAdults > 20 years
https://www.cdc.gov/nchs/data/hestat/obesity-adult-17-18/obesity-adult.htm
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BMI: <18.5 18.5-24.9 25.0-29.9 30.0-34.9 >35 >40
Underweight Normal Overweight Obesity I Obesity II Obesity III
Weight Classifications by Body Mass Index (BMI)
https://www.cdc.gov/healthyweight/assessing/index.html
Begins at BMI > 25 kg/m2
Eligibility starts for
MEDICATIONSBMI >27 kg/m2
Eligibility starts for
SURGERYBMI >30 kg/m2
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BMI: <18.5 18.5-24.9 25.0-29.9 30.0-34.9 >35 >40
Underweight Normal Overweight Obesity I Obesity II Obesity III
Anti-obesity Drug Treatment Criteria by BMI
Apovian CM, et al. Obesity (Silver Spring). 2019;27(2):190-204.
BMI >27 kg/m2
with ≥1 comorbidityBMI >30 kg/m2
with no comorbidities
Begins at BMI > 27
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BMI: <18.5 18.5-24.9 25.0-29.9 30.0-34.9 >35 >40
Underweight Normal Overweight Obesity I Obesity II Obesity III
Bariatric Surgery Criteria by BMI
with Diabetes or Metabolic Syndrome
with ≥1 severe obesity-associated
comorbidity
with Diabetes or Metabolic Syndrome
with no comorbidities
Apovian CM, Aronne LJ, Bessesen D, et al. J Clin Endocrinol Metab. 2015 Feb;100(2):342-62.ASMBS Statements/Guidelines | Volume 14, Issue 8, p1071-1087, August 01, 2018
Begins at BMI > 30
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Designation of Obesity as a Disease
1. ASMBS, TOS, ASBP, AACE Joint Statement. Obesity is a disease: leading obesity groups agree. June 19, 2013.
http://asmbs.org/2013/06/obesity-is-a-disease-leading-obesity-groups-agree/. Accessed September 11, 2013.
2. American Medical Association. AMA Resolution No. 420 (A-13). June 19, 2013.
www.ama-assn.org/assets/meeting/2013a/a13-addendum-refcomm-d.pdf.
Medical Associations and Societies1
World / National Health Organizations1,2
• American Association of Clinical Endocrinologists
• American Academy of Family Physicians
• American College of Cardiology
• American College of Surgeons
• American Medical Association
• American Society for Reproductive Medicine
• American Urological Association
• The Endocrine Society
• The Obesity Society
• The Society for Cardiovascular Angiography and Interventions
• World Health Organization
• Food and Drug Administration
• National Institutes of Health
Obesity is a disease: leading obesity groups agree
June 19
2013
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Consequences of Obesity
• Individuals with obesity are at
increased risk for multiple physical
and psychological morbidities
• Obesity also has adverse effects
on quality of life, disability, and
productivity
• Economic burden of obesity is
borne by patients, health care
providers, insurers, and taxpayers
Kabiri M, et al. Obesity. 2020;28:429-436.
Memory/cognitive problems
Sleep problems
Hypertension
Type 2 diabetes
Tumors/cancer
Fertility problems
Osteoarthritis
Gout and
rheumatological
problems
Dermatological problems
Gastrointestinal
Problems
Cardiovascular disease
Mental/emotional problems
Respiratory disease
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All-cause Mortality for Weight Change Patterns
For all participants, maintaining an obese
BMI from early adulthood to midlife
increased the risk of all-cause mortality
vs. stable normal weight, with an HR of 2.17 (95% CI, 1.85-2.53)
• Weight gain from a normal to overweight BMI was
not associated with risk, normal-obese (HR, 1.32;
95% CI, 1.15-1.52)
• Overweight to obese (HR, 1.47; 95% CI, 1.28-1.69)
weight changes were associated with elevated
mortality risks
JAMA Network Open. 2020;3(8):e2013448.
Estimated 12.4% OF EARLY DEATHS
may be attributable to having weight in
excess of the normal BMI range at any
point between early and mid-adulthood (95% CI, 8.1%-16.5%)
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Neuronal and hormonal pathways influencing food intake and satiety in the brain
Srivastava G and Apovian CM. Nat Rev Endocrinol. 2018 Jan;14(1):12-24.
161.Yu JH et al. Diabetes Metab J. 2012;36(6):391-398.2.Mendieta-Zerón H et al. Gen Comp Endocrinol. 2008;155:481-495.
CNS, central nervous system
PfC, prefrontal cortex NAc, nucleus accumbens
VTA, ventral tegmental area
PP, pancreatic polypeptide
CCK, cholecystokinin; GLP-1, glucagon-like peptide 1
OXM, oxyntomodulin
PYY, peptide YY.
Primarily based on data from animal studies. Appetite Stimulating
Appetite Suppressing
Adapted with permission from Mendieta-Zerón H et al.2
Complex Peripheral Signals are Integrated into CNS Systems to Regulate Body Weight
Peripheral signals
are relayed to brain
systems via blood
and vagus nerve 1,2
Brain systems (homeostatic and
reward) receive and integrate
peripheral and other CNS
signals (eg, dopamine,
serotonin)1,2
Leptin, insulin, and ghrelin are integrated
directly into hypothalamus
VTA
Striatum
PfC
Hypothalamus
NAc
Hindbrain
Peripheral signals
are released
by pancreas,
gastrointestinal
system, and
adipose tissue1,2
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Obesity Associated with Hypothalamic Injury in Rodents and Humans• Rodent models of obesity, induced by consuming high-fat diet (HFD), are
characterized by inflammation both in peripheral tissues and hypothalamic areas critical for energy homeostasis
• Unlike inflammation in peripheral tissues, which develops as a consequence of obesity, hypothalamic inflammatory signaling was evident in both rats and mice within 1 to 3 days of HFD onset, prior to substantial weight gain
• Both reactive gliosis and markers suggestive of neuron injury were evident in the hypothalamic arcuate nucleus of rats and mice within the first week of HFD feeding
• Evidence of increased gliosis in the mediobasal hypothalamus of obese humans, as assessed by MRI
Thaler PT, et al. J Clin Invest. 2012 Jan 3;122(1):153-62. doi: 10.1172/JCI59660. Epub 2011.
Findings suggest obesity is associated with neuronal injury
in a brain area crucial for body weight control
in both humans and rodent models
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Translation of Defense of the
Body Weight Set Point:
Body continues to fight against weight loss long
after dieting has stopped
• 2009, 50 obese men and women
• Men 233 lbs/average Women 200 lbs/average
• Extreme low-calorie diet
• Optifast shakes + 2 cups of low-starch vegetables
• Total 500-550 kcal/d for eight weeks
Sumithran P et al. N Engl J Med. 2011;365:1597-1604.
• At 10 weeks: 30-lb ave. weight loss
At year one: 11-lb ave. weight regain
• Reported feeling more hungry and preoccupied
with food than before the weight loss
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14% Weight Loss Produced Changes in Eight Hormones That Encourage Weight RegainMean fasting and postprandial levels of some peripheral signals at baseline and 62 weeks
Reduced Increased
Leptin - 65%
Peptide YY
Cholecystokinin
Insulin
Amylin
Ghrelin
Pancreatic polypeptide
Gastric inhibitory
polypeptide
Measures of appetite
10-week, lifestyle-based weight loss intervention in healthy overweight and obese adults (n=34)
Led to sustained elevations in appetite stimulating hormone(s) and decreases in appetite suppressing hormones
Sumithran P et al. N Engl J Med. 2011;365:1597-1604.
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Long-Term Persistence of Hormonal
Adaptations to Weight LossChanges in Weight
from Baseline to
Week 6230-lb LOSS
11-lb GAIN
10 week weight-loss
program
Sumithran P et al. N Engl J Med. 2011;365:1597-1604.
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2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults: A Report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines and The Obesity Society
July 1, 2014
J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):2985-3023.
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• Prescribe set number of calories per day
• There is no ideal diet
• Advise obese adults who meet criteria that surgery may be an option
2013 Guidelines: Recommendations
• Use BMI to identify risk; advise patients of their risk
• Use waist circumference to identify risk; advise patients of their risk
• 3%-5% sustained weight loss reduces risk factors and risk of diabetes
J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):2985-3023.
2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults
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Prescribe a diet to achieve reduced calorie intake for obese or
overweight individuals who would benefit from weight loss, as part
of a comprehensive lifestyle intervention. Any one of the following
methods can be used to reduce food and calorie intake:
• 1,200–1,500 kcal/d for women
• 1,500–1,800 kcal/d for men (adjust for individual’s body weight);
• 500 or 750-kcal/d energy deficit
Prescribe SET NUMBER OF CALORIES/DAY
Obesity Guidelines: Recommendation 3
• Prescribe one of the evidence-
based diets that restricts certain
food types (such as high-carb
foods, low-fiber foods, or high-fat
foods) in order to create an energy
deficit by reduced food intake
2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults
Choose an evidence-based diet –there is NO IDEAL DIET
J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):2985-3023. 2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults
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Flexitarian
Diet
Best for weight loss
flexible and vegetarian
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LAGB surgeryStomach
Appetite Suppressing
DRUGSHypothalamus
DRUG:
Lipase Inhibitors (Orlistat) Intestines
Gastric Bypass, BPD
Gastric Sleeve surgeriesIntestines
Where Obesity Treatments Work
Source of photo: Mendieta-Zerón H1, López M, Diéguez
C.Gen Comp Endocrinol. 2008 Feb 1;155(3):481-95.
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0% 5% 10% 15% 20% 25% 30% 35%
Weight Loss
Problem: Treatment Gap in Mid-BMI Range
NOT EFFECTIVE enough
for many people
After Aronne L. FDA EMDAC 2010.
DIET AND LIFESTYLE
& DRUGS
Lap BandGastric Bypass BPD
Sleeve gastrectomy
Treatment
Gap
How to fill this gap?
TOO RISKY for many people
BARIATRIC SURGERY
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Rationale for Obesity Pharmacotherapy
• Obesity causes more than 200 other medical disorders that affect entire organ systems
• Accounts for ~4 million deaths worldwide and a high cardiovascular disease burden
• Prevalence is rapidly increasing
Highlights the immediate need for
early recognition and treatment
in the context of the
existing available therapeutic armature
Srivastava G and Apovian CM. Nat Rev Endocrinol. 2018 Jan;14(1):12-24.
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Medical Treatment for Obesity vs T2DM
CDC, National Center for Health Statistics, Division of Health Interview Statistics, data from the National Health Interview Survey.
Cowie CC, et al. Diabetes Care. 2009 Feb;32(2):287-94.
Samaranayake NR, et al. Ann Epidemiol. 2012 May;22(5):349-53.
0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
50%
Obesity Type 2 Diabetes
U.S
. A
du
lt P
op
ula
tio
n (
%) Adults in the U.S.
Indicated Treated
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Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline
January 15, 2015
Apovian CM, Aronne LJ, Bessesen D, et al. J Clin Endocrinol Metab. 2015 Feb;100(2):342-62.
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FDA Approval Criteria: Anti-obesity Drug
• Standard guidelines were issued in the mid-1990s
• A new drug must induce statistically significant placebo- adjusted
weight loss of:
• >5% at 1 year or
• >35% of patients should achieve >5% weight loss
(which must be at least twice that induced by placebo)
• In addition, the medication is required to show evidence of
improvement in metabolic biomarkers, including blood pressure,
lipid levels and glycemic control
www.fda.gov/downloads/Drugs/Guidances/ucm071612.pdf
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FDA Approves New Drug Treatment for Chronic
Weight Management, First Since 2014
• Approved June 04, 2021
• Indicated for chronic weight management in patients with BMI > 27 kg/m2 with at least one weight-related ailment or BMI > 30 kg/m2
• Works by mimicking GLP-1, targeting areas of the brain that regulate appetite and food intake• Dosing must be increased gradually over 16 to 20 weeks to 2.4 mg
once weekly to reduce gastrointestinal side effects
• N = >2,600 patients up to 68 weeks in four studies with >1,500 patients receiving placebo
https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-management-first-2014
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FDA Approves New Drug Treatment for Chronic
Weight Management, First Since 2014
Trial of pts without diabetes:• 46 years average age• 74% female• 231 lbs (105 kg) average body weight • 38 kg/m2 average BMI • Lost average of 12.4% initial body weight vs. placebo
Trial of pts with type 2 diabetes:• 55 years • 51% were female• 220 lbs (100 kg)• 36 kg/m2 average BMI• Lost 6.2% of initial body weight vs. placebo
https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-management-first-2014
Adverse Effects
nausea, diarrhea,
vomiting, constipation,
abdominal pain,
headache, fatigue,
dyspepsia, dizziness,
abdominal distension,
eructation,
hypoglycemia) in
patients with type 2
diabetes, flatulence,
gastroenteritis,
gastroesophageal
reflux disease
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Effects of Once-Weekly Semaglutide vs. Placebo, on Body Weight
• Significant reduction in body
weight from baseline
• –14.9% semaglutide group vs.
–2.4% placebo group
• Greater mean weight loss
• –15.3 kg semaglutide group vs.
–2.6 kg placebo group
• Greater weight loss of at least 5%
• 86.4% in semaglutide group vs.
placebo (31.5%)
Wilding JPH, et al. N Engl J Med. 2021 Mar 18;384(11):989.
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Efficacy of Current Anti-obesity Drugs
Indicated to be used as adjuncts to a reduced-calorie diet and increased physical activity for chronic weight management in adults with a BMI ≥30 kg/m2 or
those with a BMI ≥27 kg/m2 who have at least one weight-related comorbid condition such as diabetes mellitus, hypertension, hyperlipidemia or sleep apnea
Srivastava G and Apovian CM. Nat Rev Endocrinol. 2018 Jan;14(1):12-24.
Wilding JPH, et al. N Engl J Med. 2021 Mar 18;384(11):989.
7.5/46 mg for 1 year
15 mg daily for 28 wks
Maximum dose for 56 wks
3.0 mg for 56 wks
120 mg thrice daily for 1 year
Phentermine/topiramate ER(Gadde et al. 2011)
Phentermine(Aronne et al. 2013)
Naltrexone SR/bupropion SR(Greenway et al. 2010)
Liraglutide (Saxenda)package insert 2014
Orlistat(Aronne et al. 2013)
Semaglutide (Wegovy)(Wilding et al. 2021) 2.4 mg once weekly injection for 68 wks
0 1 2 3 4 5 6 7 8 9 10 11 12 13
% Estimated weight loss (drug minus placebo)
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Current Obesity Pharmacotherapy for Long-term Use
5-HT2c=serotonin; DA=dopamine; GLP-1=glucagon-like peptide-1; MOA=mechanism of action; NE=norepinephrine.
1. Yanovski SZ et al. JAMA. 2014;311:74-86. 2. Apovian CM et al. J Clin Endocrinol Metab. 2015;100:342-362.
3. Kim GW et al. Clin Pharmacol Ther. 2014;95:53-66. 4. Dietrich MO et al. Nat Rev Drug Discov. 2012;11:675-691.
Intestines
OrlistatLipase inhibitor
Phentermine/topiramateSympathomimetic amine + antiepileptic
Liraglutide and NEW Semaglutide
GLP-1 receptor agonist
Naltrexone/bupropionµ-opioid antagonist +
DA/NE reuptake inhibitor
Mesolimbic Reward System
Hypothalamus
Hypothalamus
Hypothalamus
Dorsal Vagal
complex
Mesolimbic
Reward System
Hypothalamus
Dorsal Vagal
Complex
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Pharmacotherapy Increases Magnitude and Likelihood of Weight Loss
Pucci A, et al. Can J Cardiol. 2015;31(2):142-152. Astrup A, et al. Int J Obes (Lond). 2012;36(6):843-854.
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Long-term Ongoing Therapy Needed for
Obesity Treatment
Schalles, et al. Visc Med. 2016, figure adapted by Ania Jastreboff, MD, PhD.
AOM
stopped
NEW –
borrowed from
Ivania Rizo
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Effective Ineffective
Loss of ≥5% body weight
at 3 months and
medication is
safe/tolerated
Loss of <5% body weight
at 3 months or
safety or tolerability issue
with medication
Continue medication • Discontinue medication
• Seek alternate
medication or refer for
alternative therapy
Apovian C, Aronne LJ, et al. J Clin Endocrinol Metab. 2015 2015 Feb;100(2):342-62.
Medications: Assessing Efficacy and Safety
42Ikramuddin S, et al. Lancet Diabetes Endocrinol. 2015 Jun;3(6):413-22.
Surgery: Better Weight Loss than Lifestyle and Medical MngtThe Diabetes Surgery Study Randomized Clinical Trial
7.3%
23.8%
Difference, 17%95% CI, 13-20%
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Vertical Banded Gastroplasty
Gastric Bypass
Nonadjustable or Adjustable
Surgery: Best Long-term Weight Loss Results
Sjöström L. J Intern Med. 2013 Mar;273(3):219-34.
% Weight Change: -18% mean change in body weight over 20 years
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3540
35
6055
6558
50
82 78
6268
0
10
20
30
40
50
60
70
80
90
Diabetes HTN Sleep Apnea GERD
Band Sleeve Bypass
Resolution or Improvement in Comorbidities Varies by Type of Surgery
Hutter et al. Ann Surg. 2011 Sep;254(3):410-20; discussion 420-2.
% R
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N = >28K x 3 years
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Sleeve Gastrectomy Gastric Bypass
• Average weight loss:
– 30% of total weight
• Surgery takes about 90-120 minutes
• 1-2 days in hospital
• Limits ingestion of food and changes hunger signals
• Reversible in extreme cases
Gastric Band (LAP-BAND)
• Not commonly performed as weight loss results have not been optimal in the long-term
• Our team will consider this operation on a case-by-case basis
Bariatric Surgery Procedures
• Average weight loss:
– 25% of total weight
• Surgery takes about 60 minutes
• 1 day in hospital
• Limits ingestion of food and changes hunger signals
• Non-reversible
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The Problem
Patients who undergo bariatric surgery often have:
– Inadequate weight loss (<20% of total body weight loss), or
– Weight regain post surgery (≥15% gain of initial weight loss)
Two Studies
Discern the utility of weight loss pharmacotherapy as an adjunct to bariatric surgery and tool to prevent weight regain
Stanford FC, Aronne LJ, ET AL. Surg Obes Relat Dis. 2017 Mar;13(3):491-500. Istfan NW, Apovian CM, et al. Obesity (Silver Spring). 2020 Jun;28(6):1023-1030.
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Phentermine and Topiramate Reduce theOccurrence of Rapid Weight Regain after RYGB
Phentermine and
topiramate, used
individually or in
combination, can
significantly reduce
WR after RYGB
Istfan NW, Apovian CM, et al. Obesity (Silver Spring). 2020 Jun;28(6):1023-1030.
N= 760
350 (46.1%) used AOMs
• 119 (34.0%) phentermine
• 74 (21.1%) topiramate
• 154 (44.0 %) combination
of phentermine and
topiramate
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Design
• Retrospective study 2000-2014
Setting
• 2 Academic Institutional Practices
Patients and Other Participants
• Patients who had undergone Roux-en-Y gastric bypass (RYGB) or a vertical sleeve gastrectomy (VSG) who were subsequently placed on weight loss pharmacotherapy post-operatively
• Of the 5110 charts reviewed, 319 met inclusion criteria
Interventions
• Weight loss pharmacotherapy: 15 FDA and non-FDA approved meds
Stanford FC, Aronne LJ, et al. Surg Obes Relat Dis. 2017 Mar;13(3):491-500.
Utility of Weight Loss Medications After Weight Loss Surgery
N=319 patients
• RYGB = 258
• Sleeve gastrectomy = 61
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Results• 54%, n=172 of all study patients lost ≥ 5% of their total body weight with
post-surgery weight loss pharmacotherapy
• High responders: • 30.3% (n=96) lost ≥ 10% of their total body weight
• 15% (n=49) lost ≥15% of their total body weight
• Topiramate – the only medication demonstrating statistically significant weight loss with patients being twice as likely to lose at least 10% of their weight (OR=1.9, p=0.018)
• RYGB patients were significantly more likely to lose ≥ 5% of their total body weight with the aid of weight loss medications vs. VSG patients (regardless of postop BMI)
• Total body weight loss from surgery plus weight loss pharmacotherapy
• 26.8% (SD=10.5) [4.3-60.2%] patients starting meds after weight regain
• 32.3% (SD=11.4) [8.3-56.3%] patients starting meds at their weight plateau after bariatric surgery (p=0.486)
Utility of Weight Loss Medications After Weight Loss Surgery
Stanford FC, Aronne LJ, et al. Surg Obes Relat Dis. 2017 Mar;13(3):491-500.
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Demonstration of the utility of weight loss mediation after bariatric surgery in a RYGB patient
Stanford FC, Aronne LJ, et al. Surg Obes Relat Dis. 2017 Mar;13(3):491-500.
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Long-term Weight Loss
Long-term treatment with regular supportcan be effective1-5
Weight must be managed on an ongoing basis5-9
1. Elmer PJ, et al. Annals of Internal Medicine, 144:485–495, 2006.
2. Wadden TA. Annals of Internal Medicine, 119(7):688–693, October 1993.
3. Tate DF. JAMA, 289(14):1833–1836, April 9 2003.
4. Tate DF, Wing RR, Winett RA. JAMA 285(9):1172–1177, March 7 2001.
5. Ness-Abramof R, Nabriski D, Apovian CM. The Israel Medical Association Journal, 6:760–765, December 2004.
6. Wadden TA, Brownell KD, Foster GD. Journal of Consulting and Clinical Psychology, 70(3):510–525, 2002.
7. Wadden TA, Foster GD, Letizia KA. Journal of Consulting and Clinical Psychology, 62(1):165–171, 1994.
8. Wadden TA, et al. Archives of Internal Medicine, 161:218–227, 2001.
9. Wadden TA, et al. NEJM, 353(20):2111–2122, November 2005.
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Frequent Patient Follow-up is Key
JAN FEB MAR APR MAY JUNE JULY AUG SEPT OCT NOV DEC
All patients prescribed weight loss medications:
At least monthly for first 3 months
Then at least every 3 months
Centers for Medicare & Medicaid Services coverage:
Month 1 Four visits (1 per week)
Months 2-6 One visit per month
if 3 kg (6.6 lbs) lost, then:Month 7-12 One visit per month
www.cms.gov Decision Memo for Intensive Behavioral Therapy for Obesity (CAG-00423N).
15 visits per year
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Bariatric Surgical Patients Require Lifelong Follow-up Visits
Encourage All patients are encouraged to drink water long-term
Consumption of lean protein sources is encouraged
Vitamin and mineral supplementation should be reinforced at every visit to avoid micronutrient deficiencies
Routine exercise should be encouraged
• Walking is an appropriate way to start exercising
• Patients with degenerative joint disease may benefit from aquatic exercise to reduce joint pain
https://www.uptodate.com/contents/bariatric-surgery-postoperative-and-long-term-management-of-the-uncomplicated-patient
Processed snack foods and sweetened beverages are discouraged because they increase calorie intake unnecessarily
Carbonation and straws because of the risk of gastric bloating
Discourage Caffeinated beverages should be avoided because of the diuretic effect
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Successful Long-term Weight LossNational Weight Control Registry: Lifestyle Changes
• 10,000 registrants
• Maintaining 66 lb loss for 5 years
• Eat 1800 kcal/day with 27% fat
• Perform 2700 kcal/week exercise
• 40% weigh themselves daily
• 20% weekly
• Reduced TV watching
• Limit diet variety
• 78% eat breakfast
• Eat fast food once per week
• Use more artificially sweetened beverages than others of normal weight
• They are VIGILANT
Ten Year NWCR Data
• N=2886 who lost 31 kg maintained for 5 years
• Regain at end of 10 years but still lost 30% total body weight then gained to 22.6% total weight loss
• 10 year loss = 23 kg (50.6 lbs)
• Weight regain levels out from 5 years to 10
• 85% of registrants lost 20%
• 40% of registrants lost 30%
• If exercise decreased by 500 kcal per week they regain 9 kg
• If exercise is maintained they regain only 4.5% or 4.5 kg
National Weight Control Registry http://www.nwcr.ws/ Thomas JG, et al. Am J Prev Med. 2014 Jan;46(1):17-23.
56
Maintaining Weight LossNational Weight Control Registry
N=2886
Mean weight loss:
Baseline: 31.3 kg (95% CI=30.8, 31.9)
5 Years: 23.8 kg (95% CI=23.2, 24.4)
10 Years: 23.1±0.4 kg (95% CI=22.3, 23.9)
>87% were estimated to be maintaining >10% weight loss at Years 5 and 10
Better long-term outcomes with:
• Larger initial weight losses
• Longer duration of maintenance
Greater weight REGAIN associated with:
• Decreases in leisure-time physical
activity
• Decreases in dietary restraint
• Decreases in self-weighing frequency
• Increases in percent of intake from fat
and disinhibition
http://www.nwcr.ws/
Thomas JG, Bond DS, Phelan S, Hill JO, Wing RR. Am J Prev Med. 2014 Jan;46(1):17-23.
57
Percentage Weight Loss by Minutes of Physical Activity (calories per week)
Wadden TA, et al. Circulation. 2012;125:1157-70.
Total n=170
maintained 3xthe weight loss
vs. those at 150 min/wk
= >2000 kcal/wk)
= >1000 kcal/wk)
58
• Consistent finding in four 2012 meta-analyses, each summarizing 13 to 24 trials: adherence was most strongly associated with weight loss1-4
• Meta-analysis 2014: 48 trials, n = 7,286; conclusion: any diet a patient will adhere to lose weight is best5
1. Ajala O, English P, Pinkney J. Am J Clin Nutr. 2013 Mar;97(3):505-16.
2. Wycherley TP, et al. Am J Clin Nutr. 2012 Dec;96(6):1281-98.
3. Hu T, et al. Am J Epidemiol. 2012 Oct 1;176 Suppl 7:S44-54.
4. Bueno NB, et al. Br J Nutr. 2013 Oct;110(7):1178-87.
5. Johnston BC, et al. JAMA. 2014;312(9):923-933.
Adherence - Not Diet - Predicts Success
60Adapted from Aronne LJ, Segal KR. J Clin Psychiatry. 2003;64(Suppl 8):22-29. Leslie WS, et al. QJM. 2007;100(7):395-404. Messerli FH, et al. Am J Med. 2007;120(7):610-615.
Drugs That Tend to Promote Weight Gain, Weight Loss, or Are Weight Neutral
• Exenatide, liraglutide, pramlintide
• Sitagliptin
• Metformin
• Acarbose, miglitol
• Canagliflozin
Weight LOSS or Weight NEUTRAL
Diabetes Treatments
• Insulin
• Sulfonylureas
• Thiazolidinediones
Diabetes Treatments
Weight GAIN
• Antipsychotics
• Antidepressants
• Antiepileptics
• Lithium
Psychiatric/Neurologic
• Ziprasidone, aripiprazole
• Bupropion
• Topiramate, zonisamide, lamotrigine
Psychiatric/Neurologic
61
Ultra-processed FoodsMay Facilitate Overeating
• Rise in obesity and type 2 diabetes prevalence
occurred in parallel with increasingly industrialized
food system
• Large scale production of high yield, inexpensive,
agricultural “inputs” (corn, soy, wheat), refined and
processed
• Highly processed foods, with added amounts of fat
and/or refined carbohydrates (e.g., sugar, white
flour), were most likely to be associated with
behavioral indicators of addictive-like eating
• Additionally, foods with high GL were especially
related to addictive-like eating problems for
individuals endorsing elevated symptoms of “food
addiction”
Poti JM, et al. Curr Obes Rep. 2017 Dec;6(4):420-431.
Schulte EM, et al. PLoS One. 2015 Feb 18;10(2):e0117959.
How Often Food was
Selected as ProblematicTop 10 of 35
Food Ratings Based on
7-point Likert ScaleNot Problematic to Extremely
Top 10 of 35
62
• 20 inpatient adults received ultra-
processed and unprocessed diets
for 14 days each
• Diets were matched for presented
calories, sugar, fat, fiber, and
macronutrients
• Ad libitum intake was ~500
kcal/day more on ultra-processed
vs unprocessed diet
• Body weight changes were highly
correlated with diet differences in
energy intake
Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain
Hall KD, et al. Cell Metab. 2019 Jul 2;30(1):67-77.e3.
63
0% 5% 10% 15% 20% 25% 30% 35%
Weight Loss
Treatment Gap in Mid-BMI Range
NOT EFFECTIVE enough
for many people
After Aronne L. FDA EMDAC 2010.
DIET AND LIFESTYLE
& DRUGS
Lap BandGastric Bypass BPD
Sleeve gastrectomyPrior to 2012:
Orlistat Phentermine
Treatment
Gap
Drug options:Liraglutide
NEW Semaglutide
Combination Pharmacotherapy
Phen/topNalt/bup
Less Invasive Procedures
Vagal block therapyEndoscopic sleeve
The gap is being filled
New drugs and devices can reduce weight and weight-related comorbidities
TOO RISKY for many people
BARIATRIC SURGERY
64
Summary
• Overweight and obesity are measured by Body Mass Index (BMI)
• 42.4% of U.S. Adults have obesity
• 30.7% of U.S. Adults are overweight
• Lifestyle interventions can be effective with long-term follow-up
• Bariatric surgery is the most effective form of long-term weight loss
• Weight regain occurs in 17-30% of RYGB patients at two years post-op
• Anti-obesity medications are effective at increasing post-op weight loss and preventing weight regain
• New GLP-1 agonist, semaglutide, shows promise to help fill BMI-mid-range treatment gap
65
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